Method of manufacturing expansile filamentous embolization devices

ABSTRACT

An embolization device for occluding a body cavity includes one or more elongated, expansible, hydrophilic embolizing elements non-releasably carried along the length of an elongated filamentous carrier that is preferably made of a very thin, highly flexible filament or microcoil of nickel/titanium alloy. At least one expansile embolizing element is non-releasably attached to the carrier. A first embodiment includes a plurality of embolizing elements fixed to the carrier at spaced-apart intervals along its length. In second, third and fourth embodiments, an elongate, continuous, coaxial embolizing element is non-releasably fixed to the exterior surface of the carrier, extending along a substantial portion of the length of the carrier proximally from a distal tip, and optionally includes a lumenal reservoir for delivery of therapeutic agents. Exemplary methods for making these devices include skewering and molding the embolizing elements. In any of the embodiments, the embolizing elements may be made of a hydrophilic, macro-porous, polymeric, hydrogel foam material. In the second, third and fourth embodiments, the elongate embolizing element is preferably made of a porous, environmentally-sensitive, expansile hydrogel, which can optionally be made biodegradable and/or bioresorbable, having a rate of expansion that changes in response to a change in an environmental parameter, such as the pH or temperature of the environment.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a Continuation-in-Part of application Ser. No.09/867,340, filed May 29, 2001, now U.S. Pat. No. 6,602,261, issued Aug.5, 2003, which is a Continuation-in-Part of application Ser. No.09/542,145, filed Apr. 4, 2000, now U.S. Pat. No. 6,299,619, issued Oct.9, 2001, which is a Continuation-in-Part of application Ser. No.09/410,970, filed Oct. 4, 1999, now U.S. Pat. No. 6,238,403, issued May29, 2001.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

BACKGROUND OF THE INVENTION

The present invention relates to devices for the occlusion of bodycavities, such as in the embolization of vascular aneurysms and thelike, and methods for making and using such devices. More specifically,the present invention relates to a device that is inserted into a bodycavity, such as an aneurysm, to occlude the cavity by creating anembolism therein, a method for making the device, and a method forembolizing a body cavity using the device.

The occlusion of body cavities, blood vessels and other lumina byembolization is desired in a number of clinical situations. For example,the occlusion of fallopian tubes for the purposes of sterilization, andthe occlusive repair of cardiac defects, such as a patent foramen ovale,patent ductus arteriosis, and left atrial appendage and atrial septaldefects. The function of an occlusion device in such situations is tosubstantially block the flow of body fluids into or through the cavity,lumen, vessel, space or defect for the therapeutic benefit of thepatient.

Vascular embolization has been used to control vascular bleeding, toocclude the blood supply to tumors, and to occlude vascular aneurysms,particularly intracranial aneurysms. In recent years, vascularembolization for the treatment of aneurysms has received much attention.Several different treatment modalities have been employed in the priorart. U.S. Pat. No. 4,819,637—Dormandy, Jr. et al., for example,describes a vascular embolization system that employs a detachableballoon delivered to the aneurysm site by an intravascular catheter. Theballoon is carried into the aneurysm at the tip of the catheter, and isinflated inside the aneurysm with a solidifying fluid (typically apolymerizable resin or gel) to occlude the aneurysm. The balloon is thendetached from the catheter by gentle traction on the catheter. While theballoon-type embolization device can provide an effective occlusion ofmany types of aneurysms or other body cavities, it is difficult toretrieve or move after the solidifying fluid sets, and it is difficultto visualize unless it is filled with a contrast material. Furthermore,there are risks of balloon rupture during inflation and of prematuredetachment of the balloon from the catheter.

Another approach is the direct injection of a liquid polymer embolicagent into the cavity or vascular site to be occluded. One type ofliquid polymer used in the direct injection technique is a rapidlypolymerizing liquid, such as a cyanoacrylate resin, particularlyisobutyl cyanoacrylate, that is delivered to the target site as aliquid, and then is polymerized in situ. Alternatively, a liquid polymerthat is precipitated at the target site from a carrier solution has beenused. An example of this type of embolic agent is a cellulose acetatepolymer mixed with bismuth trioxide and dissolved in dimethyl sulfoxide(DMSO). Another type is ethylene vinyl alcohol dissolved in DMSO. Oncontact with blood, the DMSO diffuses out, and the polymer precipitatesout and rapidly hardens into an embolic mass that conforms to the shapeof the aneurysm. Other examples of materials used in this “directinjection” method are disclosed in the following U.S. Pat. No.4,551,132—Pasztor et al.; U.S. Pat. No. 4,795,741—Leshchiner et al.;U.S. Pat. No. 5,525,334—Ito et al.; and U.S. Pat. No. 5,580,568—Greff etal.

The direct injection of liquid polymer embolic agents has provendifficult in practice. For example, migration of the polymeric materialfrom the aneurysm and into the adjacent blood vessel has presented aproblem. In addition, visualization of the embolization materialrequires that a contrasting agent be mixed with it, and selectingembolization materials and contrasting agents that are mutuallycompatible may result in performance compromises that are less thanoptimal. Furthermore, precise control of the deployment of the polymericembolization material is difficult, leading to the risk of improperplacement and/or premature solidification of the material. Moreover,once the embolization material is deployed and solidified, it isdifficult to move or retrieve.

Another approach that has shown promise is the use of thrombogenicmicrocoils. These microcoils may be made of a biocompatible metal alloy(typically, platinum and tungsten) or a suitable polymer. If made ofmetal, the coil may be provided with Dacron fibers to increasethrombogenicity. The coil is deployed through a microcatheter to thevascular site. Examples of microcoils are disclosed in the followingU.S. Pat. No. 4,994,069—Ritchart et al.; U.S. Pat. No. 5,133,731—Butleret al.; U.S. Pat. No. 5,226,911—Chee et al.; U.S. Pat. No.5,312,415—Palermo; U.S. Pat. No. 5,382,259—Phelps et al.; U.S. Pat. No.5,382,260—Dormandy, Jr. et al.; U.S. Pat. No. 5,476,472—Dormandy, Jr. etal.; U.S. Pat. No. 5,578,074—Mirigian; U.S. Pat. No. 5,582,619—Ken; U.S.Pat. No. 5,624,461—Mariant; U.S. Pat. No. 5,645,558—Horton; U.S. Pat.No. 5,658,308—Snyder; and U.S. Pat. No. 5,718,711—Berenstein et al.

The microcoil approach has met with some success in treating smallaneurysms with narrow necks, but the coil must be tightly packed intothe aneurysm to avoid shifting that can lead to recanalization.Microcoils have been less successful in the treatment of largeraneurysms, especially those with relatively wide necks. A disadvantageof microcoils is that they are not easily retrievable; if a coilmigrates out of the aneurysm, a second procedure to retrieve it and moveit back into place is necessary. Furthermore, complete packing of ananeurysm using microcoils can be difficult to achieve in practice.

A specific type of microcoil that has achieved a measure of success isthe Guglielmi Detachable Coil (“GDC”), described in U.S. Pat. No.5,122,136—Guglielmi et al. The GDC employs a platinum wire coil fixed toa stainless steel delivery wire by a solder connection. After the coilis placed inside an aneurysm, an electrical current is applied to thedelivery wire, which electrolytically disintegrates the solder junction,thereby detaching the coil from the delivery wire. The application ofthe current also creates a positive electrical charge on the coil, whichattracts negatively-charged blood cells, platelets, and fibrinogen,thereby increasing the thrombogenicity of the coil. Several coils ofdifferent diameters and lengths can be packed into an aneurysm until theaneurysm is completely filled. The coils thus create and hold a thrombuswithin the aneurysm, inhibiting its displacement and its fragmentation.

The advantages of the GDC procedure are the ability to withdraw andrelocate the coil if it migrates from its desired location, and theenhanced ability to promote the formation of a stable thrombus withinthe aneurysm. Nevertheless, as in conventional microcoil techniques, thesuccessful use of the GDC procedure has been substantially limited tosmall aneurysms with narrow necks.

Still another approach to the embolization of an abnormal vascular siteis the injection into the site of a biocompatible “hydrogel,” such aspoly (2-hydroxyethyl methacrylate) (“pHEMA” or “PHEMA”); or a polyvinylalcohol foam (“PAF”). See, e.g., Horák et al., “Hydrogels inEndovascular Embolization. II. Clinical Use of Spherical Particles”,Biomaterials, Vol. 7, pp. 467–470 (November, 1986); Rao et al.,“Hydrolysed Microspheres from Cross-Linked Polymethyl Methacrylate”, J.Neuroradiol., Vol. 18, pp. 61–69 (1991); Latchaw et al., “Polyvinyl FoamEmbolization of Vascular and Neoplastic Lesions of the Head, Neck, andSpine”, Radiology, Vol. 131, pp. 669–679 (June, 1979). These materialsare delivered as microparticles in a carrier fluid that is injected intothe vascular site, a process that has proven difficult to control.

A further development has been the formulation of the hydrogel materialsinto a preformed implant or plug that is installed in the vascular siteor other body cavity by means such as a microcatheter. See, e.g., U.S.Pat. No. 5,258,042—Mehta. These types of plugs or implants are primarilydesigned for obstructing blood flow through a tubular vessel or the neckof an aneurysm, and they are not easily adapted for precise implantationwithin a sac-shaped vascular structure, such as an aneurysm, so as tofill substantially the entire volume of the structure.

U.S. Pat. No. 5,823,198—Jones et al. discloses an expansible PVA foamplug that is delivered to the interior of an aneurysm at the end of aguidewire. The plug comprises a plurality of pellets or particles thatexpand into an open-celled structure upon exposure to the fluids withinthe aneurysm so as to embolize the aneurysm. The pellets are coated witha blood-soluble restraining agent to maintain them in a compressed stateand attached to the guidewire until delivered to the aneurysm. Becausethere is no mechanical connection between the pellets and the guidewire(other than the relatively weak temporary bond provided by therestraining agent), however, premature release and migration of some ofthe pellets remains a possibility.

There has thus been a long-felt, but as yet unsatisfied need for adevice for effective occlusive treatment of aneurysms and other bodycavities, and a method that can substantially fill aneurysms and otherbody cavities of a large range of sizes, configurations, and neck widthswith an occlusive and/or thrombogenic medium with a minimal risk ofinadvertent tissue damage, aneurysm rupture or blood vessel wall damage.There has been a further need for such a method and device that alsoallow for the precise locational deployment of the medium, while alsominimizing the potential for migration away from the target location. Inaddition, a method and device meeting these criteria should also berelatively easy to use in a clinical setting. Such ease of use, forexample, should preferably include a provision for good visualization ofthe device during and after deployment in a body cavity, lumen oraneurysm.

SUMMARY OF THE INVENTION

Broadly, an embolization device, according to a first aspect of thepresent invention, comprises one or more expansible, hydrophilicembolizing elements non-releasably carried along the length of afilamentous carrier. In a first preferred embodiment, the carrier is asuitable length of very thin, highly flexible filament ofnickel/titanium alloy (Nitinol). A plurality of embolizing elements arespaced along the length of the carrier and are separated from each otheron the carrier by radiopaque spacers in the form of highly flexiblemicrocoils made of platinum or platinum/tungsten alloy, as in thethrombogenic microcoils of the prior art, as described above.

In a second preferred embodiment, the carrier comprises a continuouslength of highly flexible, hollow microcoil made of a biocompatiblemetal (preferably platinum or platinum/tungsten alloy), with an optionalcore in the form of a continuous length of thin, highly flexible metalwire, preferably of a shape memory metal alloy such as Nitinol.Alternatively, the carrier may be a suitable length of flexible wire,cable, braid, or other construction that yields the desired flexibility.The carrier is preferably made of a biocompatible metal so as to bevisible by means of X-rays or other visualization techniques known inthe art, but it also may be made of a suitable polymer that is visible(or is rendered visible) through any of the known visualization methods.The carrier should have sufficient column strength to allow the deviceto be pushed through a microcatheter.

In the second preferred embodiment, an elongate, continuous, coaxialembolizing element is non-releasably fixed to the exterior surface ofthe carrier, extending along a substantial portion of the length of thecarrier proximally from a distal tip.

In a third exemplary embodiment of an embolization device, the carriercomprises an elongated, filamentous carrier, and the embolizing elementcomprises a coaxial member of an expansile, hydrophilic polymer, orhydrogel, encapsulating at least a portion of the carrier's length. In avariant incorporating a tubular carrier, such as an tubular braid or theflexible, hollow microcoil described above, the coaxial polymer memberis formed such that the lumen of the carrier is substantially void ofthe polymer, thereby defining an axial reservoir in the carrier. Thereservoir constitutes a chamber in which therapeutic agents, e.g.,medications, can be placed for delivery to a patient via implantation ofthe device in a cavity in the patient's body.

A fourth exemplary embodiment of the embolization device is similar inmost respects to the third embodiment described above, except that, inone possible variant thereof in which the carrier comprises a flexibletube, the hydrophilic polymer of the coaxial embolizing memberencapsulating the carrier also substantially fills the lumen of thecarrier, such that the entire surface of the encapsulated portion of thecarrier is in contact with the polymer of the embolizing member and noreservoir is created in the carrier.

A first exemplary embodiment of a method for making the third embodimentof the embolization device comprises the provision of a softened,elongated embolizing member of hydrogel supported in a tubular holder.In one possible embodiment of the method, a stiff, elongated supportmandrel is inserted coaxially in the lumen of a tubular carrier, such asa helical coil, to straighten and stiffen it, and the soft polymermember is then coaxially skewered with the carrier-and-mandrel, suchthat the polymer member coaxially encapsulates at least a portion of thelength of the carrier. The skewered polymer member is then ejected fromthe tubular holder and dehydrated in a hygroscopic bath, e.g., alcohol,to remove water from, and thereby shrink, the coaxial polymer embolizingmember to a size suitable for passage through the lumen of a catheter.

After dehydration, the polymer member is treated, e.g., in an acid bath,to set the rate of hydration of the polymer, and hence, the rate ofexpansion of the member, in an aqueous environment, e.g., blood, inresponse to the level of a physical parameter of the environment, e.g.,its temperature or pH level. After the hydration rate of the device isset, it is washed to remove any processing impurities, dried by heating,e.g., in an oven, and then packaged in a sterile container.

A second exemplary embodiment of a method for making the fourthembodiment of the embolization device comprises the provision of a moldhaving an elongated cavity therein. An elongated filamentous carrier,which may comprise a tubular carrier, as above, is disposed coaxiallywithin the cavity of the mold. In one advantageous variant in which atightly-coiled helical carrier is employed, the carrier is elasticallystretched along its axis, such that the coils are held spaced apart fromeach other by the mold before disposition therein. In another possiblevariant, the coils of a helical carrier are formed permanently spacedapart, i.e., without being elastically stretched in the mold. In yetanother possible variant, a mandrel is inserted in the lumen of atubular carrier, in a manner similar to that described above inconnection with the first method.

After the carrier is disposed coaxially within the cavity of the mold, aquantity of a softened, expansile, hydrophilic polymer is transferredinto the mold under pressure, such that the polymer is molded by thecavity into an embolization member that coaxially encapsulates at leasta portion of the length of the carrier. In those variants in which thecarrier comprises a tubular carrier that is not internally supported bya lumenal mandrel, the polymer is also caused to flow into the lumen ofthe carrier, substantially filling it.

After the polymer member is molded onto the carrier, the device isreleased from the mold, which enables the adjacent coils of anelastically stretched helical carrier to spring back axially intocontact with one another through the still-soft polymer member. In thosevariants incorporating a tubular carrier internally supported by alumenal mandrel, the mandrel is removed to define a lumenal reservoir inthe device for the disposition of therapeutic agents, as in the firstexemplary method above. Indeed, the post-molding processes applied tothe device are substantially the same as those applied to the device inthe first method embodiment described above, including dehydration ofthe coaxial member, adjustment of its rate of hydration, and thewashing, drying and packaging of the device.

The second exemplary method embodiment of the invention is thus capableof making substantially the same embodiments of the embolization deviceas are made by the first method embodiment, including those with anaxial reservoir, as well as other variants of the device, includingthose having no axial reservoir, and in which the entire surface,including any internal surface, of the encapsulated portion of thecarrier is in contact with the polymer of the expansile, coaxialembolizing member.

In both the first and second exemplary methods, the lumenal supportmandrel can be removed from the carrier at any stage of the processafter the skewered or molded coaxial member is ejected from the holderor mold and before the dried and finished device is packaged. Removal ofthe mandrel creates a lumenal reservoir in the carrier that, asdescribed above, can be used as a reservoir for the delivery oftherapeutic agents, e.g., medications, blood cells, and the like, to apatient via the device. Thus, one possible embodiment of a method fordelivering a therapeutic agent to a patient may comprise making anembolization device having an axial reservoir in accordance with eitherthe first or second exemplary methods, disposing a therapeutic agent inthe reservoir of the device, and implanting the device in a body cavityof the patient.

Moreover, in both the third and fourth exemplary embodiments of thedevice, the flexibility, size, and lubricity of the hydrophilic polymerof the coaxial member, and hence, the device itself, all increase withthe degree of hydration of the polymer. In accordance with one exemplaryembodiment of this invention, the rate of hydration of the polymer in anaqueous environment is, as described above, set during manufacture to aspecific value in response to a corresponding specific level of aphysical parameter of the environment, e.g., its pH level.

Thus, in one possible embodiment of a method for preparing a fullydehydrated device for insertion into a body cavity via a catheter, thedry device is first immersed in an aqueous medium, e.g., a salinesolution, having a relatively low pH level, such that the rate ofhydration of the coaxial polymer member in the medium is correspondinglyslow. This increases the flexibility and lubricity of the device suchthat it can be easily inserted into and moved through the lumen of thecatheter and into the body cavity, but at a rate that is slow enough toafford the physician ample time to implant the device without allowingit to expand to a size that cannot be inserted into or moved easilythrough the catheter. However, once the device is emplaced in thecavity, its rate of hydration increases substantially in response to theincreased pH level of the surrounding physiological aqueous environment,i.e., blood or plasma, such that the coaxial embolizing member of thedevice then expands correspondingly rapidly to occlude the cavity.

In yet other embodiments of the embolization device incorporatingembolizing elements of hydrogel, the formulation of the polymer of thecoaxial member can be modified to incorporate polymers that degrade, orbreak down, in the body after a period of time in response to, e.g.,hydrolysis or enzymatic action, into simpler molecular constituents thatcan be absorbed by the patient's body and/or eliminated from it aswaste. Thus, in another possible embodiment of the device incorporatinga hydrogel embolizing member, the member can be made such that it isbiodegradable and/or bioresorbable in the patient's body.

In either of the first two preferred embodiments, the embolizingelements may be made of a hydrophilic, macroporous, polymeric, hydrogelfoam material, in particular a swellable foam matrix formed as amacroporous solid comprising a foam stabilizing agent and a polymer orcopolymer of a free radical polymerizable hydrophilic olefin monomercross-linked with up to about 10% by weight of a multiolefin-functionalcross-linking agent. Such a material is described in U.S. Pat. No.5,750,585—Park et al., the disclosure of which is incorporated herein byreference. The material may be modified, or provided with additives, tomake the implant visible by conventional imaging techniques.

In the second, third and fourth preferred embodiments, the elongatecoaxial embolizing element is preferably made of a porous,environmentally-sensitive, expansile hydrogel, of the type described inprior co-pending U.S. patent application Ser. No. 09/804,935, assignedto the assignee of this application and of the invention disclosed andclaimed herein. application Ser. No. 09/804,935 (the disclosure of whichis incorporated herein by reference) discloses hydrogels that experiencean increase in lubricity and undergo controlled volumetric expansion ata rate that changes in response to changes in such environmentalparameters as pH or temperature. These hydrogels are prepared by forminga liquid mixture that contains (a) at least one monomer and/or polymer,at least a portion of which is sensitive to changes in an environmentalparameter; (b) a cross-linking agent; and (c) a polymerizationinitiator. If desired, a porosigen (e.g., NaCl, ice crystals, orsucrose) may be added to the mixture, and then removed from theresultant solid hydrogel to provide a hydrogel with sufficient porosityto permit cellular ingrowth.

The controlled rate of expansion is provided through the incorporationof ethylenically unsaturated monomers with ionizable functional groups(e.g., amines, carboxylic acids). For example, if acrylic acid isincorporated into the crosslinked network, the hydrogel is incubated ina low pH solution to protonate the carboxylic acids. After the excesslow pH solution is rinsed away and the hydrogel dried, the hydrogel canbe introduced through a microcatheter filled with saline atphysiological pH or with blood. The hydrogel cannot expand until thecarboxylic acid groups deprotonate. Conversely, if an amine-containingmonomer is incorporated into the crosslinked network, the hydrogel isincubated in a high pH solution to deprotonate the amines. After theexcess high pH solution is rinsed away and the hydrogel dried, thehydrogel can be introduced through a microcatheter filled with saline atphysiological pH or with blood. The hydrogel cannot expand until theamine groups protonate.

Alternatively, in the second preferred embodiment, the elongate coaxialembolizing element may be in the form of a stretch-resistant outer layerapplied to the exterior of the carrier along a substantial portion ofthe length of the carrier. The stretch-resistant outer layer ispreferably formed of an expansile material, such as those describedabove, but it may also be formed of any stretch-resistant, biocompatiblepolymer, such as, for example, polyurethane, polyester,polytetrafluoroethylene (PTFE), nylon, polymethylmethacrylate (PMMA),and silicone.

A second aspect of the present invention is a method for embolizing abody cavity or a vascular site, comprising, in the preferred embodimentthe steps of: (a) passing a microcatheter intravascularly so that itsdistal end is introduced into a target vascular site; (b) passing avaso-occlusive device through the microcatheter into the target vascularsite so that the vaso-occlusive device assumes a three-dimensionalconfiguration that fills a portion of the volume of the target vascularsite; (c) providing a vascular embolization device comprising at leastone expansible embolizing element non-releasably connected to afilamentous carrier; (d) passing the embolization device through themicrocatheter so that it emerges from the distal end of themicrocatheter and into the target vascular site; and (e) expanding theembolizing element or elements in situ so that at least about 30%, andpreferably more than about 40%, of the total the volume of the targetvascular site is filled, while maintaining the connection between theembolizing element or elements and the carrier.

Preferably, the vaso-occlusive device is of the type that is initiallyin the form of an elongate, flexible, filamentous element for deliverythrough the microcatheter, and that assumes a three-dimensional geometryupon installation in the target vascular site. One such device is theabove-described GDC (U.S. Pat. No. 5,122,136—Guglielmi et al., thedisclosure of which is incorporated herein by reference). Other suchdevices are described in, for example, U.S. Pat. No. 5,766,219—Horton;U.S. Pat. No. 5,690,671—McGurk et al.; and U.S. Pat. No. 5,911,731—Phamet al., the disclosure of which are incorporated herein by reference.Still other types of occlusive devices known in the art may also performsatisfactorily in this method.

In an alternative embodiment of the method of the present invention, themethod comprises the steps of: (a) deploying an intravascular device toa position in a blood vessel adjacent to a target vascular site; (b)providing a vascular embolization device comprising at least oneexpansible embolizing element non-releasably connected to a filamentouscarrier; (c) passing a microcatheter intravascularly so that the distalend of the microcatheter passes through the intravascular device intothe target vascular site; (d) passing the embolization device throughthe microcatheter so that it emerges from the distal end of themicrocatheter into the target vascular site; and (e) expanding theembolizing element or elements in situ substantially to fill the volumeof the target vascular site while maintaining the connection between theembolizing element or elements and the carrier.

It is understood that the step of providing the embolization device mayfollow the step of passing the microcatheter intravascularly.

In this alternative embodiment of the method aspect of the presentinvention, the intravascular device may be of the type disclosed in U.S.Pat. No. 5,980,514—Kupiecki et al., the disclosure of which isincorporated herein by reference. This intravascular device comprises afilamentous element that is introduced by a microcatheter to thejuncture of an aneurysm or the like, and that then assumes theconfiguration of a coil adjacent the neck of the aneurysm.

In some instances, the step of passing a vaso-occlusive device or anintravascular device through the microcatheter to the target vascularsite may be omitted.

The embolization bodies or elements, in the preferred embodiment, havean initial configuration in the form of small, substantially cylindrical“micropellets” of small enough outside diameter to fit within themicrocatheter. The bodies are hydrophilically expansible into anexpanded configuration in which they substantially conform to and fillthe vascular site.

The present invention provides a number of significant advantages.Specifically, the present invention provides an effective body cavity orvascular embolization device that can be deployed within a cavity orvascular site with excellent locational control, and with a lower riskof vascular rupture, tissue damage, or migration than with prior artdevices. Furthermore, the embolization device effects a conformal fitwithin the site that promotes effective embolization, and yet itsability to be delivered to the site through a microcatheter facilitatesprecise and highly controllable deployment. In addition, the essentiallyfilamentous initial configuration of the embolization device, whereby itreadily conforms to the interior dimensions of the target site, allowsit to be used effectively to embolize body cavities having a widevariety of sizes, configurations, and (in the particular case ofaneurysms) neck widths. These and other advantages will be readilyappreciated from the detailed description that follows.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an elevational view of a vascular embolization device inaccordance with a first preferred embodiment of the invention;

FIG. 2 is a cross-sectional view taken along line 2—2 of FIG. 1;

FIG. 3 is a cross-sectional view taken along line 3—3 of FIG. 2;

FIGS. 4 through 7 are semischematic views showing the steps in a methodof embolizing a vascular site (specifically, an aneurysm) in accordancewith one embodiment of the embolizing method aspect of the presentinvention;

FIG. 8 is a detailed perspective view of mechanism by which theembolization device of the present invention is preferably attached tothe distal end of a deployment instrument;

FIG. 9 is a detailed perspective view, similar to that of FIG. 8,showing the embolization device of the present invention after it hasbeen separated from the deployment instrument;

FIGS. 10, 11, and 12 are semischematic views showing steps that, inaddition to those illustrated in FIGS. 4–7, constitute a method ofembolizing a vascular site in accordance with a preferred embodiment ofthe embolizing method aspect of the present invention;

FIG. 13 is a semischematic view showing a step in a method of embolizinga vascular site in accordance with an alternative embodiment of theembolizing method aspect of the present invention;

FIG. 14 is an elevational view, partially in section, of an embolicdevice in accordance with a second preferred embodiment of theinvention, showing the device in its normal or non-expanded state;

FIG. 15 is a cross-sectional view taken along line 15—15 of FIG. 14;

FIG. 16 is a detailed axial cross-sectional view of a portion of thedevice shown in FIG. 14;

FIG. 17 is a view similar to that of FIG. 16, showing the device of FIG.14 in its expanded state after deployment in a vascular site;

FIG. 18 is a view similar to that of FIG. 15, showing the device of FIG.14 in its expanded state after deployment in a vascular site;

FIG. 19 is a partial axial cross-sectional view of a first modified formof an embolic device in accordance with the second preferred embodimentof the present invention, showing the device in its normal ornon-expanded state;

FIG. 20 is a view similar to that of FIG. 19, showing the device of FIG.19 in its expanded state after deployment in a vascular site;

FIG. 21 is a partial axial cross-sectional view of a second modifiedform of an embolic device in accordance with the second preferredembodiment of the present invention, showing the device in its normal ornon-expanded state;

FIG. 22 is a view similar to that of FIG. 21, showing the device of FIG.21 in its expanded state after deployment in a vascular site;

FIG. 23 is a detailed axial cross-sectional view of a third modifiedform of an embolic device in accordance with the second preferredembodiment of the present invention;

FIG. 24 is a cross-sectional elevation view of a soft, expandedhydrophillic polymer embolizing element in accordance with a firstexemplary method for making a third exemplary embodiment of anembolization device in accordance with the invention;

FIG. 25 is a cross-sectional elevation view of the embolizing element ofFIG. 24 being inserted into a tubular holder;

FIG. 26 is a cross-sectional elevation view of the embolizing element ofFIG. 25 being coaxially skewered by a helical carrier internallysupported by a lumenal mandrel;

FIG. 27 is a cross-sectional elevation view of the embolizing element ofFIG. 26 after being completely skewered by the helical carrier andlumenal mandrel;

FIG. 28 is a cross-sectional elevation view of the skewered embolizingelement of FIG. 27 being ejected from the tubular holder to define anunfinished embolization device in accordance with the third exemplaryembodiment thereof;

FIG. 29 is a cross-sectional elevation view of the embolization deviceof FIG. 28 being dehydrated in a bath of a desiccant to shrink theembolizing element thereof;

FIG. 30 is a cross-sectional elevation view of the embolization deviceof FIG. 29 immersed in a bath of an acid to adjust the rate of hydrationof the embolizing element in response to a level of a physical parameterof an aqueous environment;

FIG. 31 is a cross-sectional elevation view of the embolization deviceof FIG. 30 being baked in an oven to dry the embolizing element thereof;

FIG. 32 is an elevational view of the finished embolization device inaccordance with the third exemplary embodiment thereof, with the lumenalmandrel FIG. 26 remaining in place;

FIG. 33 is a cross-sectional elevation view of the embolization deviceof FIG. 32;

FIG. 34 is an enlarged, partial cross-sectional view into theembolization device of FIG. 33, as revealed by the section taken thereinalong the lines 34—34;

FIG. 35 is an enlarged partial cross-sectional view similar to that ofFIG. 34, showing an axial reservoir defined in the embolization deviceby removal of the lumenal mandrel therefrom;

FIG. 36 is a cross-sectional elevation view of a fourth exemplaryembodiment of an embolization device in accordance with the inventionbeing molded in accordance with a second exemplary embodiment of amethod for making the device in accordance with the invention;

FIG. 37 is an enlarged, partial cross-sectional view into the nascentembolization device of FIG. 36, as revealed by the section taken thereinalong the lines 37—37, showing a carrier of the device;

FIG. 38 is an enlarged, partial cross-sectional view similar to that ofFIG. 37, showing the carrier being encapsulated in a polymer;

FIG. 39 is an elevational view of one variant of the fourth exemplaryembodiment of the embolization device;

FIG. 40A is an enlarged, partial cross-sectional view into theembolization device of FIG. 39, as revealed by the section taken thereinalong the lines 40—40, showing one possible variant thereof in which thecoils of a helically coiled carrier are spaced close together;

FIG. 40B is a view similar to that of FIG. 40A, showing another variantin which the coils of the carrier are spaced apart from each other;

FIG. 41 is an elevational view of another variant of the fourthexemplary embodiment of the embolization device, showing a lumenalmandrel in the carrier of the device;

FIG. 42A is an enlarged, partial cross-sectional view into theembolization device of FIG. 41, as revealed by the section taken thereinalong the lines 42—42, showing one possible variant thereof in which thecoils of a helically coiled carrier are spaced close together and thelumenal mandrel is removed to define an axial reservoir in the carrier;

FIG. 42B is a view similar to that of FIG. 42A, showing another variantin which the coils of the carrier are spaced apart from each other;

FIG. 43 is schematic elevation view of a method and apparatus formeasuring the flexibility of an embolization device; and,

FIG. 44 is an enlarged, partial cross-sectional detail view of theembolization device being measured in FIG. 43, as revealed by theencircled detail 44 therein.

DETAILED DESCRIPTION OF THE INVENTION

The Embolization Device: First Preferred Embodiment.

A vascular embolization device 10, in accordance with a first preferredembodiment of the present invention, is shown in FIGS. 1, 2 and 3. Inthe preferred embodiment, the embolization device 10 comprises aplurality of embolizing bodies, each configured as a substantiallycylindrical “micropellet” 12, located at spaced intervals along afilamentous carrier 14. The number of micropellets 12 will vary,depending on the length of the carrier 14, which, turn, will depend onthe size of the vascular site to be embolized. For a large vascularsite, for example, eight to twelve micropellets may be used, although aneven larger number may be used if necessary. In some applications (e.g.,very small aneurysms), as few as one or two micropellets may be used.

Also carried on the carrier 14 is a plurality of highly flexiblemicrocoil spacers 16, each of which is disposed between and separates apair of micropellets 12. The carrier 14 has a distal portion on which iscarried a relatively long distal microcoil segment 18 that is retainedin place by a distal retention member 20. The carrier 14 has a proximalportion on which is carried a relatively long proximal microcoil segment22. The proximal end of the device 10 is terminated by a hydrogellinkage element 24, to be described below. The spacers 16, the distalmicrocoil segment 18, and the proximal microcoil segment 22 are allhighly flexible, and they are preferably made of platinum orplatinum/tungsten wire, which has the advantages of being biocompatibleand radiopaque. The micropellets 12 are non-releasably carried on thecarrier 14. They may be fixed in place on the filamentous carrier 14,either mechanically or by a suitable biocompatible, water-insolubleadhesive, or they may be simply strung loosely on the carrier 14 betweensuccessive spacers 16.

The micropellets 12 are preferably formed of a biocompatible,macroporous, hydrophilic hydrogel foam material, in particular awater-swellable foam matrix formed as a macroporous solid comprising afoam stabilizing agent and a polymer or copolymer of a free radicalpolymerizable hydrophilic olefin monomer cross-linked with up to about10% by weight of a multiolefin-functional cross-linking agent. Asuitable material of this type is described in U.S. Pat. No.5,570,585—Park et al., the disclosure of which is incorporated herein byreference.

Another suitable material for the micropellets 12 is a porous hydratedpolyvinyl alcohol (PVA) foam gel prepared from a polyvinyl alcoholsolution in a mixed solvent consisting of water and a water-miscibleorganic solvent, as described, for example, in U.S. Pat. No.4,663,358—Hyon et al., the disclosure of which is incorporated herein byreference. Other suitable PVA structures are described in U.S. Pat. No.5,823,198—Jones et al. and U.S. Pat. No. 5,258,042—Mehta, thedisclosures of which are incorporated herein by reference. Anothersuitable material is a collagen foam, of the type described in U.S. Pat.No. 5,456,693—Conston et al., the disclosure of which is incorporatedherein by reference. Still another suitable material is PHEMA, asdiscussed in the references cited above. See, e.g., Horák et al., supra,and Rao et al., supra.

The preferred foam material, as described in the above-referenced patentto Park et al., has a void ratio of at least about 90%, and itshydrophilic properties are such that it has a water content of at leastabout 90% when fully hydrated. In the preferred embodiment, each of theembolizing micropellets 12 has an initial diameter of not more thanabout 0.5 mm prior to expansion in situ, with an expanded diameter of atleast about 3 mm. To achieve such a small size, the micropellets 12 maybe compressed to the desired size from a significantly larger initialconfiguration. The compression is performed by squeezing or crimping themicropellets 12 in a suitable implement or fixture, and then “setting”them in the compressed configuration by heating and/or drying. Each ofthe micropellets 12 is swellable or expansible to many times (at leastabout 25 times, preferably about 70 times, and up to about 100 times)its initial (compressed) volume, primarily by the hydrophilic absorptionof water molecules from an aqueous solution (e.g., resident blood plasmaand/or injected saline solution), and secondarily by the filling of itspores with blood. Also, the micropellets 12 may be coated with awater-soluble coating (not shown), such as a starch or a suitablepolymer, to provide a time-delayed expansion. Another alternative is tocoat the micropellets 12 with a temperature-sensitive coating thatdisintegrates in response to normal human body temperature. See, e.g.,U.S. Pat. No. 5,120,349—Stewart et al. and U.S. Pat. No.5,129,180—Stewart.

The foam material of the embolizing micropellet 12 may advantageously bemodified, or provided with additives, to make the device 10 visible byconventional imaging techniques. For example, the foam can beimpregnated with a water-insoluble radiopaque material such as bariumsulfate, as described by Thanoo et al., “Radiopaque HydrogelMicrospheres”, J. Microencapsulation, Vol. 6, No. 2, pp. 233–244 (1989).Alternatively, the hydrogel monomers can be copolymerized withradiopaque materials, as described in Horák et al., “New RadiopaquePolyHEMA-Based Hydrogel Particles”, J. Biomedical Materials Research,Vol. 34, pp. 183–188 (1997).

The micropellets 12 may optionally include bioactive or therapeuticagents to promote thrombosis, cellular ingrowth, and/orepithelialization. See, e.g, Vacanti et al., “Tissue Engineering: TheDesign and Fabrication of Living Replacement Devices for SurgicalReconstruction and Transplantation,” The Lancet (Vol. 354, Supplement1), pp. 32–34 (July, 1999); Langer, “Tissue Engineering: A New Field andIts Challenges,” Pharmaceutical Research, Vol. 14., No. 7, pp. 840–841(July, 1997); Persidis, “Tissue Engineering,” Nature Biotechnology, Vol.17, pp. 508–510 (May, 1999).

The filamentous carrier 14 is preferably a length of nickel/titaniumwire, such as that marketed under the trade name “Nitinol”. Wire of thisalloy is highly flexible, and it has an excellent “elastic memory”,whereby it can be formed into a desired shape to which it will returnwhen it is deformed. In a preferred embodiment of the invention, thewire that forms the carrier 14 has a diameter of approximately 0.04 mm,and it is heat-treated to form a multi-looped structure that may assumea variety of three-dimensional shapes, such as a helix, a sphere, or anovoid when unconstrained (as disclosed, for example, in U.S. Pat. No.5,766,219—Horton, the disclosure of which is incorporated herein byreference). Preferably, the intermediate portion of the carrier 14(i.e., the portion that includes the micropellets 12) and the proximalportion (that carries the proximal microcoil segment 22) are formed intoloops having a diameter of approximately 6 mm, while the distal portion(that carries the distal microcoil segment 18) may have a somewhatgreater diameter (e.g., approximately 8–10 mm). The carrier 14 may beformed of a single wire, or it may be formed of a cable or braidedstructure of several ultra-thin wires.

In another embodiment, the carrier 14 may be made of a thin filament ofa suitable polymer, such as a PVA, that is formed in a looped structure.The polymer may be impregnated with a radiopaque material (e.g., bariumsulfate or particles of gold, tantalum, or platinum), or it may enclosea core of nickel/titanium wire. Alternatively, the carrier 14 may beconstructed as a “cable” of thin polymer fibers that includes fibers ofan expansile polymer, such as polyvinyl alcohol (PVA), at spacedintervals to form the micropellets 12.

Still another alternative construction for the carrier 14 is acontinuous length of microcoil. In such an embodiment, the micropellets12 would be attached at spaced intervals along the length of the carrier14.

As shown in FIGS. 1, 8, and 9, the hydrogel linkage element 24 isadvantageously made of the same material as the micropellets 12. Indeed,the most proximal of the micropellets 12 may function as the linkageelement 24. The linkage element 24 is attached to the proximal end ofthe carrier 14 by a suitable biocompatible adhesive. The purpose of thelinkage element 24 is to removably attach the device 10 to a deploymentinstrument 30 (FIGS. 8 and 9). The deployment instrument 30 comprises alength of platinum or platinum/tungsten microcoil outer portion 32 witha flexible wire core 34 of the same or a similar metal. The deploymentinstrument 30 has a distal portion 36 at which the microcoil outerportion 32 has coils that are more distantly-spaced (i.e., have agreater pitch).

As shown in FIG. 8, the device 10 is initially attached to thedeployment instrument 30 by means of the linkage element 24.Specifically, the linkage element 24 is installed, in a compressedstate, so that it encompasses and engages both the proximal end of theembolization device 10 and the distal portion 36 of the deploymentinstrument 30. Thus, in the compressed state, the linkage element 24binds the deployment instrument 30 and the embolization device 10together. As shown in FIG. 9, and as will be described in detail below,after the device 10 is deployed in a vascular site, the linkage element24 expands greatly, thereby loosening its grip on the distal portion 36of the deployment instrument 30, and thus allowing the embolizationdevice 10 to be separated from the deployment instrument 30 by pullingthe latter proximally out of and away from the linkage element 24.

The Embolization Device: Second Preferred Embodiment. FIGS. 14 through23 illustrate an embolization device in accordance with a secondpreferred embodiment of the present invention. Referring first to FIGS.14 through 17, a device 100 in accordance with this second embodimentcomprises an elongate, flexible, filamentous carrier 102 on which anexpansile embolizing element 104 is non-releasably carried. The carrier102 is preferably formed from a continuous length of hollow microcoil106, made from a suitable metal such as platinum, gold, tungsten, ortantalum, or a metallic alloy, such as stainless steel or Nitinol. Ofthese materials, platinum and Nitinol are preferred. The microcoil isformed with tightly-packed coils, so that there is little or no spacingbetween adjacent coils. The carrier 102 may also include a filamentouscore 108 extending axially through the microcoil 106. The core 108 is athin metal wire, preferably made of a shape memory metal such asNitinol. The device 100 includes a distal portion comprising an outercoil 110 coaxially surrounding the microcoil 106, and terminating in arounded distal tip 112. A hydrogel linkage element (not shown), of thetype described above and illustrated in FIGS. 8 and 9, mayadvantageously be provided at the proximal end of the carrier.

The carrier 102 may, alternatively, be made of any of the materialsdescribed above with respect to the carrier of the first preferredembodiment. While it is preferably in the configuration of a microcoil,it may also be formed as a single strand of metal wire or polymericfilament, or as a multi-strand braid or cable of metal wire or polymericfilament. The carrier should have a column strength sufficient to allowit to be pushed through a microcatheter, as mentioned above.

The expansile embolizing element 104 is advantageously formed as ahydrogel layer covering a substantial portion of the length of thecarrier 102. The embolizing element 104 may be made of any of thematerials used in the embolizing elements of the above-described firstpreferred embodiment. Advantageously, however, the embolizing element104 of this second embodiment is preferably formed of a porous,environmentally-sensitive, expansile hydrogel, of the type described inprior co-pending U.S. patent application Ser. No. 09/804,935 (thedisclosure of which is incorporated herein by reference). For theconvenience of the reader, a brief description of a suitable formulationof a preferential hydrogel is set forth below.

Specifically, the hydrogels described in the above-referenced priorapplication are of a type that experience an increase in lubricity andundergo controlled volumetric expansion in an aqueous environment at arate that changes in response to changes in a physical parameter of theenvironment, such as its pH or temperature. These hydrogels are preparedby forming a liquid mixture that contains (a) at least one monomerand/or polymer, at least a portion of which is sensitive to changes inan environmental parameter; (b) a cross-linking agent; and (c) apolymerization initiator. If desired, a porosigen (e.g., NaCl, icecrystals, or sucrose) may be added to the mixture, and then removed fromthe resultant solid hydrogel to provide a hydrogel with sufficientporosity to permit cellular ingrowth. The controlled rate of expansionis provided through the incorporation of ethylenically unsaturatedmonomers with ionizable functional groups (e.g., amines, carboxylicacids). For example, if acrylic acid is incorporated into thecrosslinked network, the hydrogel is incubated in a low pH solution toprotonate the carboxylic acids. After the excess low pH solution isrinsed away and the hydrogel dried, the hydrogel can be introducedthrough a microcatheter filled with saline at physiological pH or withblood. The hydrogel cannot expand until the carboxylic acid groupsdeprotonate. Conversely, if an amine-containing monomer is incorporatedinto the crosslinked network, the hydrogel is incubated in a high pHsolution to deprotonate amines. After the excess high pH solution isrinsed away and the hydrogel dried, the hydrogel can be introducedthrough a microcatheter filled with saline at physiological pH or withblood. The hydrogel cannot expand until the amine groups protonate.

More specifically, in a preferred formulation of the hydrogel, themonomer solution is comprised of ethylenically unsaturated monomers, anethylenically unsaturated crosslinking agent, a porosigen, and asolvent. At least a portion, preferably 10%–50%, and more preferably10%–30%, of the monomers selected must be pH sensitive. The preferred pHsensitive monomer is acrylic acid. Methacrylic acid and derivatives ofboth acids will also impart pH sensitivity. Since the mechanicalproperties of hydrogels prepared exclusively with these acids are poor,a monomer to provide additional mechanical properties should beselected. A preferred monomer for providing mechanical properties isacrylamide, which may be used in combination with one or more of theabove-mentioned pH sensitive monomers to impart additional compressivestrength or other mechanical properties. Preferred concentrations of themonomers in the solvent range from 20% w/w to 30% w/w.

The crosslinking agent can be any multifunctional ethylenicallyunsaturated compound, preferably N,N′-methylenebisacrylamide. Ifbiodegradation of the hydrogel material is desired, a biodegradablecrosslinking agent should be selected. The concentrations of thecrosslinking agent in the solvent should be less than about 1% w/w, andpreferably less than about 0.1% w/w.

The porosity of the hydrogel material is provided by a supersaturatedsuspension of a porosigen in the monomer solution. A porosigen that isnot soluble in the monomer solution, but is soluble in the washingsolution can also be used. Sodium chloride is the preferred porosigen,but potassium chloride, ice, sucrose, and sodium bicarbonate can also beused. It is preferred to control the particle size of the porosigen toless than about 25 microns, more preferably less than about 10 microns.The small particle size aids in the suspension of the porosigen in thesolvent. Preferred concentrations of the porosigen range from about 5%w/w to about 50% w/w, more preferably about 10% w/w to about 20% w/w, inthe monomer solution. Alternatively, the porosigen can be omitted and anon-porous hydrogel can be fabricated.

The solvent, if necessary, is selected based on the solubilities of themonomers, crosslinking agent, and porosigen. If a liquid monomer (e.g.2-hydroxyethyl methacrylate) is used, a solvent is not necessary. Apreferred solvent is water, but ethyl alcohol can also be used.Preferred concentrations of the solvent range from about 20% w/w toabout 80% w/w, more preferably about 50% w/w to about 80% w/w.

The crosslink density substantially affects the mechanical properties ofthese hydrogel materials. The crosslink density (and hence themechanical properties) can best be manipulated through changes in themonomer concentration, crosslinking agent concentration, and solventconcentration. The crosslinking of the monomer can be achieved throughreduction-oxidation, -radiation, and heat. Radiation crosslinking of themonomer solution can be achieved with ultraviolet light and visiblelight with suitable initiators or ionizing radiation (e.g. electron beamor gamma ray) without initiators. A preferred type of crosslinkinginitiator is one that acts via reduction-oxidation. Specific examples ofsuch red/ox initiators that may be used in this embodiment of theinvention are ammonium persulfate andN,N,N′,N′-tetramethylethylenediamine.

After the polymerization is complete, the hydrogen is washed with water,alcohol or other suitable washing solution(s) to remove theporosigen(s), any unreacted, residual monomer(s) and any unincorporatedoligomers. Preferably this is accomplished by initially washing thehydrogel in distilled water.

As discussed above, the control of the expansion rate of the hydrogel isachieved through the protonation/deprotonation of ionizable functionalgroups present on the hydrogel network. Once the hydrogel has beenprepared and the excess monomer and porosigen have been washed away, thesteps to control the rate of expansion can be performed.

In embodiments where pH sensitive monomers with carboxylic acid groupshave been incorporated into the hydrogel network, the hydrogel isincubated in a low pH solution. The free protons in the solutionprotonate the carboxylic acid groups on the hydrogel network. Theduration and temperature of the incubation and the pH of the solutioninfluence the amount of control on the expansion rate. Generally, theduration and temperature of the incubation are directly proportional tothe amount of expansion control, while the solution pH is inverselyproportional. It has been determined that the water content of thetreating solution also affects the expansion control. In this regard,the hydrogel is able to expand more in the treating solution and it ispresumed that an increased number of carboxylic acid groups areavailable for protonation. An optimization of water content and pH isrequired for maximum control on the expansion rate. After the incubationis concluded, the excess treating solution is washed away and thehydrogel material is dried. The hydrogel treated with the low pHsolution has been observed to dry down to a smaller dimension than theuntreated hydrogel. This is a desired effect, since delivery of thesehydrogel materials through a microcatheter is desired, as discussedbelow.

If pH sensitive monomers with amine groups were incorporated into thehydrogel network, the hydrogel is incubated in high pH solution.Deprotonation occurs on the amine groups of the hydrogel network at highpH. The duration and temperature of the incubation, and the pH of thesolution, influence the amount of control on the expansion rate.Generally, the duration, temperature, and solution pH of the incubationare directly proportional to the amount of expansion control. After theincubation is concluded, the excess treating solution is washed away andthe hydrogel material is dried.

In yet other embodiments of the embolization device incorporatingembolizing elements comprising hydrogel, the formulation of the hydrogelpolymer of the member can be modified to incorporate polymers thatdegrade, or break down, in the body after a period of time in responseto, e.g., hydrolysis or enzymatic action, into simpler molecularconstituents that can be absorbed by the patient's body and/oreliminated from it as waste. Polymers suitable for incorporation intothe embolization device for this purpose include those described in:“Types of Biodegradable Hydrogels,” Biodegradable Hydrogels for DrugDelivery, K. Park et al., Technomic Publishing 1993, pp. 35–66; U.S.Pat. No. 6,316,522—Loomis et al.; U.S. Pat. No. 6,224,892—Searle; U.S.Pat. No. 6,201,065—Pathan et al. The disclosures of the foregoingreferences are incorporated herein by this reference. Thus, in otherpossible embodiments of the embolization device incorporating anexpansile polymer embolizing member, the member can be made such that itis biodegradable and/or bioresorbable in the patient's body, where suchproperties are clinically indicated.

As shown in FIG. 14, an embolic device 100 in accordance with thissecond embodiment may include more than one elongate expansileembolizing elements 104. Also, if desired for a particular application,two or more embolizing devices 100 can be joined end-to-end at ajuncture 114 formed by a weld or a solder joint.

FIGS. 14, 15, and 16 show the device 100 with the embolizing elements104 in their non-expanded state. Each embolizing element 104 assumes atubular configuration in the form of a coating or layer on the exteriorsurface of the carrier 102. FIGS. 17 and 18 show an embolizing element104 in its expanded state after deployment in a vascular site. If madefrom the environmentally-sensitive hydrogel described above, theexpansion is a reaction to the pH and/or temperature experienced in thevascular site. The expansion begins between about 1 minute and about 30minutes after deployment, and preferably about 15 minutes afterdeployment. This delayed expansion allows the physician sufficient timeto reposition and even withdraw the device without the need for arestraining agent, encapsulating layer, or a non-aqueous carrier fluid.When fully expanded, the embolizing element 104 has an expanded volumethat is between about two times and about 100 times its non-expandedvolume, and preferably between about 3 times and about 25 times itsnon-expanded volume.

A first modification of this second preferred embodiment is shown inFIGS. 19 and 20. As shown, a modified embolic device 100′ comprises anelongate, flexible, filamentous carrier. The carrier comprises anelongate, hollow microcoil 106′ that is similar to the microcoil 106shown in FIGS. 14–17, except that it has significant spaces betweenadjacent coils. Like the device 100 of FIGS. 14–17, the carrier of thedevice 100′ may advantageously include a central axial core 108′, formedof a thin, flexible wire. An expansile embolizing element 104′, made ofany of the above-described hydrogels, is formed on the carrier so thatit resides between adjacent coils of the microcoil 106′, therebyencapsulating them. FIG. 19 shows the embolizing element 104′ in itsnon-expanded state, while FIG. 20 shows it in its expanded state, afterdeployment.

Another modification of the second preferred embodiment is shown inFIGS. 21 and 22. An embolic device 100″ in accordance with this versioncomprises an elongate, filamentous carrier, preferably in the form of ahollow, flexible microcoil 106″. Although the carrier is shown without awire core, it is understood that a wire core may be included, asdescribed above. In this version, a plurality of expansile embolizingelements 120 are formed as fibers or threads that are attached to themicrocoil 106″ at spaced-apart intervals along its length. Each of theexpansile embolizing elements 120 is preferably made of anenvironmentally-sensitive hydrogel, of the type described in the priorco-pending application described above, although the hydrogel describedin the U.S. Pat. No. 5,750,585—Park et al., supra, may also be used, aswell as any of the other hydrogel materials described above inconnection with the first preferred embodiment of the embolic device.FIG. 21, shows the embolizing elements 120 in their non-expanded state,while FIG. 22 shows them in their expanded state after deployment.

Still another modification of the second preferred embodiment is shownin FIG. 23. An embolic device 100′″ in accordance with this versioncomprises an elongate, filamentous carrier, preferably in the form of ahollow, flexible microcoil 106′″. The carrier may include a wire core,although one is not shown in the drawing. This version includes anelongate coaxial embolizing element 104′″ that is in the form of astretch-resistant outer layer applied to the exterior of the microcoil106′″ along a substantial portion of the its length. Thestretch-resistant outer layer is preferably formed of an expansilepolymer, such as those described above, but it may also be formed of anystretch-resistant, biocompatible polymer, such as, for example,polyurethane, polyester, polytetrafluoroethylene (PTFE), nylon,polymethylmethacrylate (PMMA), and silicone.

The Embolization Device: Third Exemplary Embodiment and First Method forMaking It: A third exemplary embodiment of a device 300 for occluding abody cavity is illustrated in FIGS. 32–35, and a first exemplaryembodiment of a method for making the third embodiment of the device 300is illustrated in FIGS. 24–31.

As shown in FIG. 32, the embolization device 300 comprises an elongated,filamentous carrier 302, and an embolizing element comprising a coaxialmember 304 of an expansile, hydrophilic polymer, or hydrogel, describedin detail above, encapsulating at least a portion of the length of thecarrier.

Although the coaxial polymer embolizing member 304 is shown in thefigures as having a substantially cylindrical shape, it should beunderstood that the member, and indeed, the carrier encapsulated withinit, can have a wide variety of other cross-sectional shapes, e.g.,polygonal, longitudinally grooved, and the like, depending on theparticular application at hand.

The carrier 302 may, as in the first and second embodiments of devicedescribed above, comprise either an elongated strand of a flexible,biocompatible material, e.g., a platinum wire, or a flexible tube.However, in a variant incorporating a tubular carrier, such as a tubularbraid or the flexible, hollow microcoil 302 described above andillustrated in the exemplary embodiment of FIG. 32, the coaxial polymermember 304 is formed on the carrier by the method described below suchthat the hollow lumen of the carrier is substantially void of thepolymer, thereby defining an axial reservoir 306 in the carrier, asshown in FIG. 35. The reservoir 306 in the carrier 302 constitutes areservoir in which therapeutic agents, in either a liquid or a solidform, can be disposed for delivery to a patient via emplacement of thedevice 300 in a body cavity of the patient, as described below.

A first exemplary embodiment of a method for making the exemplary thirdembodiment of the device 300 is illustrated in FIGS. 24–31 of thedrawings. With reference to FIG. 24, the method begins with theprovision of a softened, elongated member 304 of a expansile,hydrophilic polymer, such as hydrogel. Since the softness of the polymeris a function of the degree of its hydration, the elongated member 304can be softened by immersing it in a bath of water until it reaches thedesired state of softness, viz., about that of fully cooked pasta.

When hydrated to the desired state, the softened polymer member 304 isinserted into a tubular holder 308 such that the member is radiallyconfined and axially restrained in the holder, as illustrated in FIG.25. In one possible embodiment, this is effected by inserting apartially hydrated member 304 into the holder 308, then immersing bothin a bath of water until the member expands in the holder to the desiredstate of support and retention therein.

As illustrated in FIGS. 26 and 27, after the softened polymer member 304is retained in the holder 308, the member is then coaxially skeweredwith an elongated, flexible, filamentous carrier 302 such that thepolymer member coaxially encapsulates at least a portion of the lengthof the carrier. In one possible embodiment in which the carrier 302comprises an elongated strand, such as a wire, this procedure iseffected by simply pushing one end of the wire coaxially through thesoftened member 304, provided the wire is sufficiently straight andstiff, or if not, then by attaching a first end of the wire to the eyeof a needle (not illustrated), then forcing the needle through thesoftened member coaxially, such that the carrier is pulled coaxiallythrough the member by the needle.

In another possible embodiment of the method in which the carriercomprises a flexible tube, such as the helical microcoil 302 illustratedin the figures, a stiff, elongated support mandrel 316 is first insertedcoaxially in the lumen of the carrier to straighten and stiffen it, asshown in FIG. 26. The soft polymer member 304 is then coaxially skeweredwith the carrier supported on the mandrel, such that the polymer membercoaxially encapsulates at least a portion of the length of the carrier,as shown in FIG. 27.

After the skewering process, the skewered polymer member 304 and carrier302 are ejected from the tubular holder 308 to define a partiallyfinished embolization device 300. In the exemplary embodimentillustrated in FIG. 28, this ejection is effected by placing a nozzle310 against one end of the tubular holder 308 and forcing the skeweredmember 304 out of the other end of the holder with hydraulic pressureapplied through the nozzle.

After the device 300 is removed from the holder 308, the lumenal mandrel316 may be withdrawn from the device to define the axial reservoir 306in the carrier 302, as shown in FIG. 35, or alternatively, the mandrelmay be left in the carrier to support the device during the subsequentprocesses applied to it. As shown in FIG. 29, the first of thesepost-skewering processes comprises dehydrating the coaxial polymermember 304 of the device 300, e.g., by immersion of the device in ahygroscopic medium, e.g., an alcohol bath 312, to remove water from, andthereby shrink, the coaxial polymer member radially from its originalsoft, expanded size, represented by the phantom outline 314 in FIG. 29,to a thinner, drier member more suitable for passage through the lumenof a catheter, as illustrated.

After the dehydration process, the polymer member 304 of the device 300is washed, then treated, e.g., by immersing the device in an acid bath318 of a selected strength and for a selected period of time, asillustrated in FIG. 30, to set the rate of hydration of the polymer, andhence, the rate of expansion, of the coaxial polymer member 304, in anaqueous environment, e.g., blood or plasma, in response the level of aphysical parameter of that environment, e.g., its temperature or pHlevel, as described above. After the hydration rate of the device 300has been set, it is washed, preferably in a solution of water andalcohol, to remove any processing impurities, and then dried by heating,e.g., by baking in an oven 320, as illustrated in FIG. 31. The dry,finished embolization device 300 may then be packaged in a sterilecontainer for storage or shipment.

The Embolization Device: Fourth Exemplary Embodiment and Second Methodfor Making It: A fourth exemplary embodiment of an embolization device400 for occluding a body cavity is illustrated in FIGS. 39–42, and asecond exemplary embodiment of a method for making the fourth embodimentof the device 400 is illustrated in FIGS. 36–38.

As illustrated in FIGS. 39 and 41, respectively, two possible variantsof the fourth exemplary embodiment of embolization device 400 bothcomprise, as in the case of the third exemplary embodiment 300 describedabove, an elongated, filamentous carrier 402, and a coaxial member 404of an expansile, hydrophilic polymer, or hydrogel, encapsulating atleast a portion of the length of the carrier. Further, in both variants,the carrier 402 may, like the third embodiment above, comprise either anelongated strand of a flexible, biocompatible material, e.g., platinumwire, or a flexible tube.

However, in contrast to the third embodiment of the device 300 above, inthe first variant incorporating a tubular carrier, such as the flexible,hollow microcoil 402 described above and illustrated in the exemplaryembodiment of FIG. 39, the coaxial polymer member 404 is formed on thecarrier by the method described below in such a way that the lumen ofthe carrier is substantially occupied by the polymer, whereby no axialreservoir is created in the carrier, as illustrated in the enlargedcross-sectional views thereof of FIGS. 40A and 40B.

Alternatively, in the second variant of the device 400 illustrated inFIG. 41, which also incorporates a tubular carrier, viz., a flexible,hollow microcoil 402, the coaxial polymer member 404 can be formed onthe carrier in a variation of the method described below such that thehollow lumen of the carrier is substantially void of the polymer,thereby defining an axial reservoir 406 in the carrier, as illustratedin FIGS. 42A and 42B, in a manner similar to that created in the thirdembodiment 300 described above and illustrated in FIG. 35.

The second exemplary embodiment of a method for making the exemplaryfourth embodiment of the device 400 is illustrated in FIGS. 36–38.Referring to FIG. 36, the method begins with the provision of a mold 408having an elongated cavity 410 therein. The mold 408 may also include avent 412 for venting air from the cavity 410 during the moldingoperation described below.

An elongated filamentous carrier 402, which may comprise a tubular,helically coiled carrier, as above, is disposed coaxially within thecavity 410 of the mold 408. In one possible variant of the method inwhich a tightly-coiled helical carrier 402 is employed, the carrier iselastically stretched along its axis, such that the coils 414 of thecarrier are held spaced apart from each other while the carrier isdisposed in the mold 408, as shown in the enlarged cross-sectional viewof FIG. 37. In another possible variant, the coils 414 of a helicalcarrier 402 are formed such that they are spaced apart permanently,i.e., without stretching the carrier in the mold 408. In yet anotherpossible variant of the method, a support mandrel 416 is insertedcoaxially in the lumen of a helical carrier 402, which may have eitherclosely spaced or spaced-apart helical coils 414, in a manner similar tothat described above in connection with the first method, before thecarrier is disposed in the cavity 410 of the mold 408.

When the carrier 402 is disposed in the cavity 410 of the mold 408, aquantity of a expansile, hydrophilic polymer 418, which has beensoftened by hydration to a viscosity that is about the same as thatdescribed above in connection with the first exemplary methodembodiment, is transferred into the mold under pressure, as illustratedin FIG. 36, such that the polymer is molded by the cavity into a member404 that coaxially encapsulates at least a portion of the length of thecarrier 402, and in those variants in which the carrier comprises alumen that is not occupied by a mandrel 416, such that the polymer alsoflows into and substantially occupies the lumen of the carrier, asillustrated in the enlarged cross-sectional view of FIG. 38.

After the polymer member 404 has been molded onto the carrier 402, thepartially finished embolization device 400 is released from the mold408. The appearance of the molded device 400 is similar to thoseillustrated in FIGS. 39 and 41, except that the molded polymer member404 is still soft and swollen by hydration. Consequently, in thosevariants of the method in which a helical carrier 402 has been retainedin the mold 408 in an elastically stretched condition, this release fromthe mold causes the adjacent coils 414 of the carrier to spring backinto contact with one another through the still-soft polymer member 404,as shown in the enlarged cross-sectional view of FIG. 40A. In thosevariants of the method in which a helical carrier 402 has been retainedin the mold 408 in a permanently expanded condition, the adjacent coils414 of the carrier do not spring back elastically, but remain spacedapart in the polymer member 404 after the device is released from themold, as shown in the enlarged cross-sectional view of FIG. 40B. Ineither case, however, it may be seen that, in both of these variants ofthe method, the lumen of the carrier 402 is fully occupied by thepolymer 418 of the member 404, such that no axial reservoir is formed inthe carrier.

However, in those variants of the method incorporating a support mandrel416 inserted in the lumen of a tubular carrier 402 before the molding,such as that illustrated in FIG. 41, removal of the mandrel from themolded device 400, which may be effected at any stage after molding andbefore packaging of the device, results in a lumenal reservoir 406 beingdefined in the carrier of the device similar to that formed by the firstexemplary method described above, as illustrated in the enlargedcross-sectional views of FIG. 42A, in which the coils 414 of the helicalcarrier are shown having returned to a tightly coiled state, and FIG.42B, in which the coils of the carrier are shown in a permanentlyspaced-apart condition.

The post-molding processes applied to the fourth exemplary embodiment ofthe embolization device 400 are substantially the same as those appliedto the third exemplary embodiment of the device 300 in the firstexemplary method described above, including dehydration of the coaxialmember 404, adjustment of its rate of hydration, and the washing, dryingand sterile packaging of the device.

It may be seen from the foregoing description that, in both the firstand second exemplary methods, the lumenal support mandrel 316 or 416 canbe removed from the carrier 302 or 402 at any stage of the process afterthe skewered or molded coaxial member 304 or 404 is ejected or releasedfrom the holder 308 or mold 408, and before the dried and finisheddevice 300 or 400 is packaged. Removal of the mandrel creates an axialreservoir 306 or 406 in the carrier that, as described above, can beused as a receptacle for the delivery of therapeutic agents, e.g.,medications, blood cells, and the like, to a patient via implantation ofthe device.

A wide variety of therapeutic agents, in either liquid or solid form,can be effectively delivered via the axial cavities 306, 406 of thedevices 300, 400, and includes such agents as: drugs; growth factors;proteins; clotting agents; sclerosants; anti-infectives, such asantibiotics and antiviral agents; chemotherapeutic agents;anti-rejection agents; analgesics and analgesic combinations;anti-inflammatory agents; hormones, such as steroids; growth factors;and, other naturally derived or genetically engineered proteins,polysaccharides, glycoproteins, or lipoproteins. Thus, an exemplarymethod for delivering a therapeutic agent to a patient comprisesproviding an embolization device 300 or 400 in accordance with the thirdor fourth exemplary embodiments thereof described above, disposing atherapeutic agent in the axial reservoir 306 or 406 of the carrier 302or 402 of the device, and implanting the device in a body cavity of thepatient in accordance with one of the methods described below.

Moreover, in both the third and fourth exemplary embodiments of thedevice 300 and 400, it will be seen that the properties of thehydrophilic polymer is such that the flexibility, size, and lubricity ofthe polymer of the coaxial embolizing member 304, 404, and hence, thedevice itself, all increase with the degree of hydration of the polymer.Further, in accordance with one exemplary embodiment of this invention,the rate of hydration of the polymer in response to a physicalparameter, e.g., the pH or temperature, of an aqueous environment, canbe set at the time of device manufacture.

Thus, in one exemplary embodiment of a method for preparing a fullydehydrated device 300 or 400 for insertion into a body cavity via acatheter, as described below, the dry device is first immersed in anaqueous medium, e.g., a saline solution, having a relatively low pHlevel of about 5, such that the rate of hydration of the coaxial polymermember in the medium is correspondingly relatively slow. This increasesboth the flexibility and the lubricity of the device 300 or 400 suchthat it can easily be inserted into and pushed through the lumen of thecatheter and into the target body cavity, but at a rate that is slowenough to prevent the device from expanding so much that it cannot thenbe inserted into or moved easily through the catheter, thereby affordingthe practitioner ample time, e.g., between about 5 and 15 minutes, inwhich to implant the device in the patient. However, once the device isemplaced in the cavity, its rate of hydration increases substantially inresponse to the increased physiological pH level of the surroundingaqueous environment, e.g., blood or plasma, which have pH levels ofbetween about 7.0 and 7.5, such that the coaxial member of the devicethen rapidly expands to occlude the cavity.

Additionally, as described above, the formulation of the polymer of thecoaxial member 304 or 404 can be modified to incorporate polymers thatdegrade, or break down after a period of time by, e.g., hydrolysis orenzymatic reaction in the body cavity into simpler molecularconstituents that can be easily and safely absorbed by the body and/oreliminated from it as waste. Thus, in another possible embodiment of thedevice incorporating a coaxial embolizing member comprising hydrogel,the member can be made such that it is biodegradable and/orbioresorbable in the patient's body.

FIG. 43 illustrates a quick and convenient method known in the industryfor determining the flexibility, or conversely, the stiffness, of anembolization device in accordance with this invention, as taught in,e.g., U.S. Pat. No. 5,690,666—A. Berenstein et al. As shown in FIG. 43,an exemplary device 420 is supported on a first horizontal surface 422such that a portion 424 of the device overhangs a second horizontalsurface 426 disposed vertically below the first surface by an arbitrary,fixed height 428, and such that the unsupported end 430 of theoverhanging portion just touches the second surface.

It may be seen that, in this arrangement, the overhanging portion 424 ofthe device 420 takes on a curved shape, due to the weight of theoverhanging portion, as shown in the enlarged, partial cross-sectionaldetail view of FIG. 44, and the horizontal distance 432 between theunsupported end 430 and the supported end 434 of the overhanging portionprovides a measure of the flexibility, or conversely, the stiffness ofthe device. Thus, the stiffer the device, the longer the horizontaldistance 432 between the two ends 430 and 434, and vice-versa.

Measured in accordance with the foregoing method, and for a fixed height428 of about 0.75 in. (19.1 mm), an exemplary embolization device inaccordance with the present invention may have, by way of example andwithout limitation, a stiffness, or flexibility, as indicated by thehorizontal distance 432 between the two ends 430 and 434, of more thanabout 2.25 inches (57.2 mm) when the hydrogel is in a dry (i.e., leastflexible) state, between about 1.5 in. (38.2 mm) and 2.25 in. (57.2 mm)when the hydrogel is in a moderately hydrated (i.e., more flexible)state, and less than about 1.5 in (38.2 mm) when the hydrogel is in afully hydrated (i.e., most flexible) state.

The Method for Embolizing a Vascular Site. One method of embolizing avascular site using either the embolization device 10 (first preferredembodiment) or the embolizing device 100 (second preferred embodiment)is illustrated in FIGS. 4 through 7. This method will be described withreference to the embolic device 10 of the first preferred embodiment,but it will be appreciated that this method is equally applicable to thedevice 100 of the second preferred embodiment.

First, as shown in FIG. 4, a microcatheter 40 is threadedintravascularly, by known methods, until its distal end is locatedwithin the targeted vascular site (here, an aneurysm 42). Brieflydescribed, this threading operation is typically performed by firstintroducing a catheter guidewire (not shown) along the desiredmicrocatheter path, and then feeding the microcatheter 40 over thecatheter guidewire until the microcatheter 40 is positioned adjacent thedistal aspect of the dome of the aneurysm, as shown in FIG. 4. Thecatheter guidewire is then removed. Then, as shown in FIGS. 5 and 6, theembolization device 10, which is attached to the distal end of thedeployment instrument 30, as described above, is passed axially throughthe microcatheter 40, using the deployment instrument 30 to push thedevice 10 through the microcatheter 40 until the device 10 is clear fromthe distal end of the microcatheter 40 and fully deployed within theaneurysm 42 (FIG. 6), filling the aneurysm from its distal aspect. Thedeployment procedure is facilitated by the visualization of theembolization device 10 that is readily accomplished due to itsradiopaque components, as described above.

In the first preferred embodiment, the embolization bodies ormicropellets 12, in their compressed configuration, have a maximumoutside diameter that is less than the inside diameter of themicrocatheter 40, so that the embolization device 10 can be passedthrough the microcatheter 40. The micropellets 12 are preferablycompressed and “set”, as described above, before the device 10 isinserted into the microcatheter 40. When inserting the device 10 intothe microcatheter 40, a biocompatible, substantially non-aqueous fluid,such as polyethylene glycol, may be injected into the microcatheter 40to prevent premature expansion of the device 10 due to hydration, and toreduce friction with the interior of the microcatheter 40.

As shown in FIG. 6, when the embolization device 10 is exposed from themicrocatheter 40 into the interior of the vascular site 42, the pores ofthe embolizing bodies or micropellets 12, and of the linkage element 22,begin to absorb aqueous fluid from the blood within the vascular site 42to release their “set”, allowing these elements to begin assuming theirexpanded configuration. The expansion can be enhanced and accelerated byinjecting saline solution through the microcatheter 40. The expansion ofthe linkage element 24 allows the embolization device 10 to be separatedfrom the deployment instrument 30, as described above, and thedeployment instrument 30 can then be removed. Also, the elastic memoryof the carrier 14 causes it to resume its original looped configurationonce it is released from the confines of the microcatheter 40. Thus,almost immediately upon its release into the vascular site (aneurysm)42, the embolization device begins to occupy a significant portion ofthe volume of the aneurysm 42.

If the micropellets 12 are of a hydrophilic material, they then continueto expand in situ due to hydrophilic hydration of the material, as wellas from the filling of their pores with blood. If the embolizing bodies12 are of a non-hydrophilic material, their expansion is due to thelatter mechanism only. In either case, the result, as shown in FIG. 7,is the substantially complete filling of the interior of the aneurysm 42with the expanded embolizing bodies or micropellets 12, whereby asubstantially conformal embolizing implant 44 is formed thatsubstantially fills the interior of the aneurysm 42. The micropellets12, being non-releasably carried the carrier 14 and fixed in placethereon, stay on the carrier during their expansion. Thus, the chance ofa micropellet separating from the carrier and migrating out of thevascular site is minimized.

In the second preferred embodiment, the embolizing element 104 is notcompressed in its initial configuration. Rather, it initially has aconfiguration in which its outside diameter is small enough to passthrough the typical microcatheter. Once deployed within the targetvascular site, the embolizing element 104 expands solely by hydration.

It may be advantageous, prior to performing the procedural stepsdescribed above, preliminarily to visualize the aneurysm 42, byconventional means, to obtain a measurement (or at least anapproximation) of its volume. Then, a device 10 of the appropriate sizecan be selected that would expand to fill the measured or estimatedvolume.

A preferred method of embolizing a target vascular site using theembolization device 10 will be understood with reference to FIGS. 10–12,along with FIGS. 4–7 (discussed above). In this preferred embodiment ofthe method, the passing of a microcatheter 40 intravascularly until itsdistal end is introduced into a target vascular site (FIG. 4) isfollowed by the step of passing a vaso-occlusive device 50 through themicrocatheter 40 into the target vascular site (e.g., the aneurysm 42)so that the vaso-occlusive device 50 assumes a three-dimensionalconfiguration that fills a portion of the interior volume of the targetvascular site 42, as shown in FIG. 10. The deployed vaso-occlusivedevice 50 forms a “cage” within the aneurysm 42 that provides a matrixfor improved retention of the expansible embolizing bodies ormicropellets 12 of the embolization device 10. The embolization device10 is then passed through the microcatheter 40, as described above, andas shown in FIG. 11, to enter the aneurysm 42 within the voids left bythe vaso-occlusive device 50. Finally, the embolizing bodies ormicropellets 12 are expanded, as described above, and as shown in FIG.12, whereby a substantially conformal embolizing implant 44′ is formedthat fills a substantial portion of the interior volume of the aneurysm42. Specifically, at least about 30%, and preferably at least about 40%of the interior volume is filled, and, it is believed that in somesituations, as much as about 80% to 90% of the interior volume may befilled.

Preferably, the vaso-occlusive device 50 is of the type that isinitially in the form of an elongate, flexible, filamentous element fordelivery through the microcatheter, and that assumes a three-dimensionalgeometry (either by elastic behavior or by shape memory) uponinstallation in the target vascular site. Such devices are describe in,for example, U.S. Pat. Nos. 5,122,136—Guglielmi et al.; U.S. Pat. No.5,766,219—Horton; U.S. Pat. No. 5,690,671—McGurk et al.; and U.S. Pat.No. 5,911,731—Pham et al., the disclosures of which are incorporatedherein by reference. Still other types of vaso-occlusive devices knownin the art may also perform satisfactorily in this method. For example,a stent-like device like that shown in U.S. Pat. No. 5,980,554—Lenker etal. may be employed Alternatively, the vaso-occlusive device 50 may bedesigned or installed only to enter the space near the opening or “neck”of the aneurysm. In any case, the purpose of the vaso-occlusive device50 in this method is to present a structural framework that helps retainthe embolization device 10 in place within the target vascular site.

An alternative embodiment of the method of the present invention will beunderstood with reference to FIG. 13. In this alternative embodiment,the method includes the preliminary step of deploying an intravasculardevice 60 to a position in a blood vessel 62 adjacent to a targetvascular site 42. A microcatheter 40′ is passed intravascularly so thatits distal end passes through the intravascular device 60 into thetarget vascular site 42. The embolization device 10 is passed throughthe microcatheter 40′ so that it emerges from the distal end of themicrocatheter 40′ into the target vascular site 42, and the embolizingelements 12 are then expanded in situ, as described above, substantiallyto fill the volume of the target vascular site 42 (as shown in FIGS. 7and 12).

It is understood that the step of deploying an intravascular device to aposition in a blood vessel adjacent to a target vascular site wouldinclude any sub-steps necessary for such deployment. For example, if theintravascular device 60 is of the type disclosed in U.S. Pat. No.5,980,514—Kupiecki et al. (the disclosure of which is incorporatedherein by reference), the deployment step would comprise the sub-stepsof (i) passing of a microcatheter intravascularly so that its distal endis located adjacent the target vascular site; (ii) passing theintravascular device through the microcatheter until it emerges from thedistal end of the microcatheter; and (iii) allowing the intravasculardevice to assume a three-dimensional configuration adjacent to thetarget vascular site. In this case, either the microcatheter used fordeploying the intravascular device could be removed and then anothermicrocatheter used to install the embolization device, or theintravascular deployment microcatheter could be repositioned for theintroduction of the embolization device.

In this alternative method, the intravascular device presents anobstruction that at least partially blocks the juncture between thetarget vascular site and the blood vessel (e.g., the neck of ananeurysm). Thus, the intravascular device helps retain the embolizationdevice in its proper position within the target vascular site.

It will be apparent that the method of using the second preferredembodiment of the device will be substantially similar to theabove-described method.

Although the embolic device in accordance with the present invention hasbeen described above for use in embolizing aneurysms, other applicationswill readily suggest themselves. For example, it can be used to treat awide range of vascular anomalies, such as arteriovenous malformationsand arteriovenous fistulas. Certain tumors may also be treated by theembolization of vascular spaces or other soft tissue voids using thepresent invention. The devices may also be used to occlude fallopiantubes for the purposes of sterilization, and the occlusive repair ofcardiac defects, such as a patent foramen ovale, patent ductusarteriosis, and left-atrial-appendage and atrial-septal defects. In suchcircumstances, the occlusion device functions to substantially block theflow of body fluids into or through the cavity, lumen, vessel, space ordefect for the therapeutic benefit of the patient.

While preferred embodiments of the invention have been described above,a number of variations and modifications may suggest themselves to thoseskilled in the pertinent arts. For example, the initial shape and numberof embolizing bodies or elements may be varied, as well as the length ofthe carrier. Furthermore, other mechanisms may be found for removablyattaching the embolization device to the deployment wire. One suchalternative attachment mechanism may be a transition polymer joint thatloosens when heated by contact with blood or by a low-level electriccurrent. These and other variations and modifications are consideredwithin the spirit and scope of the invention, as described in the claimsthat follow.

1. A device for embolizing a body cavity, the device comprising: anelongated, flexible, filamentous carrier having a looped portion; and amember of an expansile, hydrophilic polymer coaxially encapsulating atleast a portion of the looped portion of the carrier.
 2. The device ofclaim 1, wherein the carrier includes an axial lumen, and wherein thepolymer of the member substantially fills the lumen of the encapsulatedportion of the carrier.
 3. The device of claim 1, wherein the carrierincludes an axial lumen having an axial reservoir therein.
 4. The deviceof claim 1, wherein the carrier comprises a filamentous element selectedfrom the group consisting of a flexible wire, helical coil, and tube. 5.The device of claim 1, wherein the coaxial member is cylindrical.
 6. Thedevice of claim 1, wherein the coaxial member comprises hydrogel.
 7. Thedevice of claim 1, wherein the coaxial member is at least one ofbiodegradable and bioresorbable.
 8. The device of claim 1, wherein thecoaxial member has a substantially greater lubricity when hydrated thanwhen dry.
 9. A device for occluding a cavity, the device comprising: anelongated, filamentous carrier having a looped portion, the carrierbeing formed of a biocompatible material having an elastic memory and anexternal surface; and a coaxial member of an expansile hydrogel formedover the carrier such that the member covers a substantial portion ofthe external surface of the looped portion of the carrier; wherein thedevice has at least one of a greater flexibility and a greater lubricitywhen the hydrogel is hydrated than when the hydrogel is dehydrated. 10.The device of claim 9, wherein an unsupported end of a portion of thedevice deflects downward under the weight of the portion and relative toan opposite, supported end of the portion about 0.75 in. (19.1 mm) when:the hydrogel is in a dry state and a horizontal distance between theopposite ends of the portion is more than about 2.25 in. (57.2 mm); thehydrogel is in a moderately hydrated state and the horizontal length isbetween about 1.5 in. (38.2 mm) and 2.25 in. (57.2 mm); and, thehydrogel is in a fully hydrated stated and the horizontal length is lessthan about 1.5 in (38.2 mm).
 11. A device for embolizing a body cavity,the device comprising: an elongated, filamentous carrier with anexternal surface, at least a portion of the carrier being a loopedportion; and a coaxial member of a hydrophilic polymer covering asubstantial portion of the external surface of the looped portion of thecarrier; wherein a physical property of the coaxial member in an aqueousenvironment is a function of time in the environment and a physicalparameter of the environment.
 12. The device of claim 11, wherein thephysical property is at least one of the flexibility and the lubricityof the member, and wherein the physical parameter of the environment isat least one of the temperature and the pH of the environment.